Table III.
Secondary outcomes
| Risk of BPD or Death | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | All | ||||||
| Outcome | Vitamin A | Control | Vitamin A | Control | Vitamin A | Control | Vitamin A | Control | Vitamin A | Control |
| Risk factors for BPD | n=105 | n=96 | n=97 | n=105 | n=104 | n=98 | n=99 | n=103 | n=405 | n=402 |
| Late-onset sepsisa | 23 (21.9) | 34 (35.4) | 29 (29.9) | 39 (37.1) | 53 (51.0) | 46 (46.9) | 47 (48.0) | 50 (48.5) | 152 (37.6) | 169 (42.0) |
| Surgical NEC | 2 (1.9) | 4 (4.2) | 5 (5.2) | 5 (4.8) | 13 (12.6) | 9 (9.2) | 7 (7.1) | 11 (10.7) | 27 (6.7) | 29 (7.2) |
| Surgical PDA closure | 3 (2.9) | 6 (6.3) | 9 (9.3) | 8 (7.6) | 16 (15.4) | 17 (17.3) | 6 (6.1) | 20 (19.4) | 34 (8.4) | 51 (12.7) |
| Signs of lung injury | 17 (16.2) | 10 (10.4) | 26 (26.8) | 24 (22.9) | 27 (26.0) | 32 (32.7) | 51 (51.5) | 40 (38.8) | 121 (29.9) | 106 (26.4) |
| Pulmonary air leakb | 4 (3.8) | 5 (5.2) | 6 (6.2) | 9 (8.6) | 7 (6.7) | 15 (15.3) | 16 (16.2) | 11 (10.7) | 33 (8.1) | 40 (10.0) |
| Pulmonary hemorrhage | 8 (7.6) | 4 (4.2) | 6 (6.2) | 7 (6.7) | 10 (9.6) | 5 (5.1) | 16 (16.2) | 15 (14.6) | 40 (9.9) | 31 (7.7) |
| PIE | 6 (5.7) | 6 (6.3) | 22 (22.7) | 14 (13.3) | 17 (16.3) | 25 (25.5) | 42 (42.4) | 26 (25.2) | 87 (21.5) | 71 (17.7) |
| Days on mechanical ventilation (d)—mean (SD)c | 13 (13), n=88 | 15 (13), n=76 | 26 (14), n=82 | 23 (15), n=88 | 36 (18), n=81 | 32 (15), n=71 | 42 (20), n=57 | 44 (18), n=66 | 28 (20), n=308 | 28 (18), n=301 |
| Days of postnatal systemic corticosteroids (d)—mean (SD)d | 14 (13), n=26 | 21 (17), n=23 | 23 (17), n=60 | 22 (21), n=53 | 27 (20), n=63 | 25 (12), n=63 | 26 (15), n=58 | 30 (19), n=67 | 24 (18), n=207 | 26 (18), n=206 |
| Vitamin A Status e | ||||||||||
| Serum retinol (μg/dl)— median, 5th-90th %ile† | 22.2 (11.6, 65.5), n=48 | 15.9 (7.7, 35.9), n=49 | 35.3 (15.5, 73.4), n=35 | 17.4 (7.1, 73.6), n=36 | 35.6 (11.8, 81.6), n=38 | 19.5 (7.7, 74.6), n=34 | 43.7 (16.9, 101.9), n=34 | 22.7 (5.6, 58.8), n=26 | 29.8 (12.9, 83.7), n=155 | 17.8 (7.4, 63.1), n=145 |
| Relative dose–response >10% —n (%)† | 11 (23.4), n=47 | 26 (54.2), n=48 | 9 (25.7), n=35 | 16 (45.7), n=35 | 8 (21.6), n=37 | 13 (38.2), n=34 | 6 (18.2), n=33 | 10 (38.5), n=26 | 34 (22.4), n=152 | 65 (45.5), n=143 |
| Respiratory Status at 36 wk d | n=102 | n=91 | n=92 | n=99 | n=88 | n=82 | n=64 | n=75 | n=346 | n=347 |
| Respiratory support—n (%) | ||||||||||
| HFV | 0(0) | 0 (0) | 0 (0) | 1 (1.0) | 0 (0) | 0 (0) | 1 (1.6) | 0 (0) | 1 (0.3) | 1 (0.3) |
| CMV | 2 (2.0) | 1 (1.1) | 6 (6.5) | 6 (6.1) | 6 (6.8) | 5 (6.1) | 9 (14.1) | 9 (12.0) | 23 (6.6) | 21 (6.1) |
| CPAPf | 3 (2.9) | 2 (2.2) | 7 (7.6) | 2 (2.0) | 7 (8.0) | 7 (8.5) | 5 (7.8) | 6 (8.0) | 22 (6.4) | 17 (4.9) |
| NC/Hood†‡ | 24 (23.5) | 35 (38.5) | 30 (32.6) | 43 (43.4) | 50 (56.8) | 46 (56.1) | 36 (56.3) | 41 (54.7) | 140 (40.5) | 165 (47.6) |
| None | 73 (71.6) | 53 (58.2) | 49 (53.3) | 47 (47.5) | 25 (28.4) | 24 (29.3) | 13 (20.3) | 19 (25.3) | 160 (46.2) | 143 (41.2) |
| FiO2—mean (SD)g | 0.51 (0.32) | 0.63 (0.35) | 0.56 (0.34) | 0.54 (0.33) | 0.56 (0.34) | 0.55 (0.33) | 0.59 (0.32) | 0.53 (0.32) | 0.56 (0.33) | 0.56 (0.33) |
| Nasal cannula flow (ml/min)—mean (SD) h,† | 350 (386) | 337 (394) | 195 (262) | 277 (296) | 300 (364) | 447 (471) | 268 (322) | 426 (408) | 278 (336) | 375 (400) |
| Mean airway pressure (cmH20)—mean (SD)i | 7.0 (0) | 8.0 (N/A) | 7.5 (1.8) | 7.9 (1.5) | 7.2 (1.5) | 9.0 (2.0) | 8.0 (2.4) | 6.2 (1.8) | 7.6 (1.9) | 7.5 (2.0) |
| Tracheostomy—n (%) | 0 (0) | 1 (1.1) | 2 (2.2) | 1 (1.0) | 2 (2.3) | 1 (1.2) | 1 (1.6) | 0 (0) | 5 (1.4) | 3 (0.9) |
| Corticosteroids—n (%) | 3 (2.9) | 7 (7.7) | 10 (10.9) | 9 (9.1) | 16 (18.2) | 5 (6.1) | 13 (20.3) | 17 (22.7) | 42 (12.1) | 38 (11.0) |
| Bronchodilators—n (%) | 10 (9.8) | 7 (7.7) | 30 (32.6) | 25 (25.3) | 24 (27.6) | 20 (24.4) | 19 (29.7) | 27 (36.0) | 83 (24.1) | 79 (22.8) |
| Diuretics—n (%) | 18 (17.6) | 17 (18.7) | 25 (27.2) | 30 (30.3) | 28 (32.2) | 23 (28.0) | 31 (48.4) | 40 (53.3) | 102 (29.6) | 110 (31.7) |
Defined as positive blood culture >72 hours after birth
Included pneumothorax, pneumopericardium, and pneumomediastinum
Mechanical ventilation includes conventional mechanical ventilation (CMV) and high-frequency ventilation (HFV) and was measured among survivors to 36 weeks’ postmenstrual age
Measured among survivors to 36 weeks’ postmenstrual age
Serum retinol level was measured for the first 300 infants to reach study day 28. Of these, 295 had complete information available to calculate a relative dose-response.
Included 2 infants who received continuous positive airway pressure (CPAP) through endotracheal tube; all others received non-invasive CPAP.
Among infants receiving any respiratory support at 36 weeks’ PMA.
Among infants on nasal cannula (NC). Reported flow rates did not exceed 2 liters per minute (2000 ml per minute). Data were not available for 15 infants.
Among infants on mechanical ventilation. Data were not available for infants receiving CPAP.
Significantly different (p<0.05) between vitamin A therapy and control groups.
Significant (p<0.05) interaction of predicted risk of bronchopulmonary dysplasia (BPD) or death on association with vitamin A therapy.
BPD=bronchopulmonary dysplasia; PDA=patent ductus arteriosus; NEC=necrotizing enterocolitis; PIE=pulmonary interstitial emphysema; FiO2 = fraction of inspired oxygen; SD = standard deviation